1. Field of the Invention
This invention resides in the field of laboratory apparatus for performing procedures that require simultaneous temperature control in a multitude of samples in a multi-receptacle sample block. In particular, this invention addresses concerns arising with the use of thermoelectric modules for temperature modulation and control.
2. Description of the Prior Art
The polymerase chain reaction (PCR) is one of many examples of chemical processes that require precise temperature control of reaction mixtures with rapid temperature changes between different stages of the procedure. PCR is a process for amplifying DNA, i.e., producing multiple copies of a DNA sequence from a single copy. PCR is typically performed in instruments that provide reagent transfer, temperature control, and optical detection in a multitude of reaction vessels such as wells, tubes, or capillaries. The process includes a sequence of stages that are temperature-sensitive, different stages being performed at different temperatures and the temperature being cycled through repeated temperature changes. In the typical PCR process, each sample is heated and cooled to three different target temperatures where the sample is maintained for a designated period of time. The first target temperature is about 95° C. which is the temperature required to separate double strands. This is followed by cooling to a target temperature of 55° C. for hybridization of the separated strands, and then heating to a target temperature of 72° C. for reactions involving the polymerase enzyme. The cycle is then repeated to achieve multiples of the product DNA, and the time consumed by each cycle can vary from a fraction of a minute to two minutes, depending on the equipment, the scale of the reaction, and the degree of automation. This thermal cycling is critical to the successful performance of the process, and is an important feature of any process that requires close control of temperature and a succession of stages at different temperatures. Many of these processes involve the simultaneous processing of large numbers of samples, each of a relatively small size, often on the microliter scale. In some cases, the procedure requires that certain samples maintained at one temperature while others are maintained at another. Laboratory equipment known as thermal cyclers have been developed to allow these procedures to be performed in an automated manner.
One of the methods for achieving temperature control over a multitude of samples in a thermal cycler or in any planar array, and also for placing segregated groups of samples at different temperatures, is by the use of thermoelectric modules. These modules are semi-conductor-based electronic components that function as small heat pumps through use of the Peltier effect, and can cause heat to flow in either direction, depending on the direction of current through the component. The many uses of thermoelectric modules include small laser diode coolers, portable refrigerators, and liquid coolers.
Thermoelectric modules are of particular interest in thermal cyclers in view of the localized temperature effect, electronic control, and rapid response that the modules offer. The modules are typically arranged edge-to-edge in a planar array to provide heating or cooling of a multitude of samples over a wide area, particularly when the samples are contained in a sample block, which is a unitary piece that has a flat undersurface and a number of wells or receptacles formed in its upper surface in a standardized geometrical arrangement. In the typical arrangement, the modules are placed under the sample block, and a heat sink, typically finned, is placed under the modules.
While the modules are highly effective and versatile, their efficiency can be compromised by a variety of factors in the construction of the cycler. The temperature changes can cause condensation on the module surfaces, for example, and the clamping apparatus that assures that the components are in full thermal contact can interfere with the heat sink fins. These and other concerns are addressed by the present invention.